Randomised trial of home-based psychosocial nursing intervention for patients recovering from myocardial infarction

BACKGROUND: Increases in life stress have been linked to poor prognosis, after myocardial infarction (MI). Previous research suggested that a programme of monthly screening for psychological distress, combined with supportive and educational home nursing interventions for distressed patients, may improve post-MI survival among men. Our study assessed this approach for both men and women. We aimed to find out whether the programme would reduce 1-year cardiac mortality for women and men. METHODS: We carried out a randomised, controlled trial of 1376 post-MI patients (903 men, 473 women) assigned to the intervention programme (n = 692) or usual care (n = 684) for 1 year. All patients completed a baseline interview that included assessment of depression and anxiety. Survivors were also interviewed at 1 year. FINDINGS: The programme had no overall survival impact. Preplanned analyses showed higher cardiac (9.4 vs 5.0%, p = 0.064) and all-cause mortality (10.3 vs 5.4%, p = 0.051) among women in the intervention group. There was no evidence of either benefit or harm among men (cardiac mortality 2.4 vs 2.5%, p = 0.94; all-cause mortality 3.1 vs 3.1%, p = 0.93). The programme's impact on depression and anxiety among survivors was small. INTERPRETATION: Our results do not warrant the routine implementation of programmes that involve psychological-distress screening and home nursing intervention for patients recovering from MI. The poorer overall outcome for women, and the possible harmful impact of the intervention on women, underline the need for further research and the inclusion of adequate numbers of women in future post-MI trials.     

In situ levels of intracellular Ca2+ and pH in avian growth plate cartilage

Interactions with the extracellular matrix, accumulation of Ca2+, formation of matrix vesicles, and regulation of tissue pH by growth plate chondrocytes all appear to be vital to endochondral calcification. Thus, the activities of Ca2+ and H+ ions in these cells, while still embedded in their organic matrix, are of great interest. Using laser confocal imaging and sensitive Ca2+ (Indo 1) and pH (BCECF) probes, cellular Ca2+ and pH were analyzed in thin sections of freshly isolated cartilage. Mean values of cytosolic Ca2+ in cells from the various zones of the growth plate were quite similar, but levels in individual cells and subcellular compartments varied significantly. Ca2+ was elevated intensely near the periphery of cells in the zones of maturation and hypertrophy, and many Ca2+ rich particles were seen in the matrix near these cells. Levels of Ca2+ within the cells varied with time. In the proliferative region, cyclical increases and decreases in Ca2+ were seen, but there was little shedding of Ca2+ rich particles. However, after repeated Ca2+ cycling, in the zones of maturation and hypertrophy, Ca2+ rich particles were shed from the cell surface, forming what appeared to be matrix vesicles. Intracellular pH levels also varied significantly within the chondrocytes and between the cells and zones. Numerous focal elevations in pH (> 8.0) were seen in central regions of the maturing and early hypertrophic cells, with lower pH (6.5-7.2) near the cell periphery of the late hypertrophic and calcifying cells. This pattern of cytoplasmic alkalinization and subsequent acidification appears to contribute to loading of Ca2+ and Pi into matrix vesicles during their formation by the chondrocytes.     

Chemoprevention trial of contralateral breast cancer with fenretinide. Rationale, design, methodology, organization, data management, statistics and accrual

The Fenretinide (4-HPR) Breast Cancer Study is a randomized multicenter clinical trial originally designed and conducted by the investigators of the Istituto Nazionale Tumori of Milan. The study is sponsored by the National Cancer Institute of Bethesda and by the Italian National Research Council. The trial was designed to evaluate the effectiveness of the synthetic retinoid 4-HPR, at a dose of 200 mg per os every day for 5 years, in reducing the incidence of contralateral breast cancer in a population of patients previously operated on for breast cancer. Between 1987 and 1993, the Istituto Nazionale Tumori of Milan and 9 other collaborating Centers enrolled 2,972 women between the ages of 30 and 70 years who had been previously operated on for T1-T2 N- M0 breast cancer. This paper describes the rationale, design, methodology, organization, data management, statistics and accrual of the participating population.     

Molecular evolution of P transposable elements in the genus Drosophila. III. The melanogaster species group

Phylogenetic relationships were determined for 76 partial P-element sequences from 14 species of the melanogaster species group within the Drosophila subgenus Sophophora. These results are examined in the context of the phylogeny of the species from which the sequences were isolated. Sequences from the P-element family fall into distinct subfamilies, or clades, which are often characteristic for particular species subgroups. When examined locally among closely related species, the evolution of P elements is characterized by vertical transmission, whereby the P-element phylogeny traces the species phylogeny. On a broader scale, however, the P-element phylogeny is not congruent with the species phylogeny. One feature of P-element evolution in the melanogaster group is the presence of more than one P-element subfamily, differing by as much as 36%, in the genomes of some species. Thus, P elements from several individual species are not monophyletic, and a likely explanation for the incongruence between P-element and species phylogenies is provided by the comparison of paralogous sequences. In certain instances, horizontal transfer seems to be a valid alternative explanation for lack of congruence between species and P-element phylogenies. The canonical P-element subfamily, which represents the active, autonomous transposable element, is restricted to D. melanogaster. Thus, its origin clearly lies outside of the melanogaster species group, consistent with the earlier conclusion of recent horizontal transfer.     

Disruption of fibronectin binding to the alpha 5 beta 1 integrin stimulates the expression of cyclin-dependent kinases and DNA synthesis through activation of extracellular signal-regulated kinase

The alpha 5 alpha 1 integrin, a fibronectin receptor, has been implicated in the control of cell growth and the regulation of gene expression. We report that disruption of ligation between alpha 5 alpha 1 and fibronectin by integrin alpha 5 subunit or fibronectin monoclonal antibodies stimulated DNA synthesis in growth-arrested FET human colon carcinoma cells. This stimulation only occurred when monoclonal antibody was added in the early G1 phase of the cell cycle after release from quiescence by fresh medium. Stimulation of DNA synthesis by alpha 5 or fibronectin antibody was concentration- and time-dependent. FET cells expressed alpha 4 beta 1 integrin (another fibronectin receptor); however, addition of anti-human integrin alpha 4 monoclonal antibody had no effect on DNA synthesis. Treatment with alpha 5 monoclonal antibody led to a marked increase in the expression of CDK4 in G1 phase of the cell cycle and consequently increased the phosphorylation of retinoblastoma protein. alpha 5 monoclonal antibody treatment increased both cyclin A- and cyclin E-associated kinase activity which was accompanied by increased protein levels of CDK2 and cyclin A. Western blotting of immunoprecipitates demonstrated increased CDK2-cyclin E and CDK2-cyclin A complexes in cells treated with alpha 5 monoclonal antibody. Furthermore, disruption of alpha 5 alpha 1/fibronectin ligation activated mitogen-activated protein kinase p44 and p42 (extracellular signal-regulated kinase 1 and 2). Pretreatment of the cells with a specific inhibitor of MEK-1, PD98059, blocked the alpha 5 monoclonal antibody-induced mitogen-activated protein kinase activity. In addition PD98059 prevented alpha 5 monoclonal antibody-induced DNA synthesis. Since alpha 5 alpha 1 ligation to fibronectin is associated with decreased growth parameters, our results indicate that ligation of alpha 5 alpha 1 integrin to fibronectin results in suppressed mitogen-activated protein kinase activity which in turn inhibits cyclin-dependent kinase activity in growth-arrested cells.